4.1 Article

The impact of folate status and folic acid supplementation on the micronucleus frequency in human erythrocytes

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ELSEVIER SCIENCE BV
DOI: 10.1016/j.mrgentox.2005.11.009

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folic acid; folate; micronucleus; flow cytometer; human erythrocytes; human reticulocytes; vitamin B12; homocysteine

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Folic acid has a well-documented stabilising effect on chromosomes. A correlation between folate status and chromosome stability in humans has been reported in studies that were restricted to certain subpopulations, e.g., folate-deficient persons. The goal of the present investigation was to clarify if there also is a correlation between folate status and chromosome stability among individuals without any folate deficiency. The method used here is the recently developed flow cytometry-based micronucleus assay in human transferrin-positive reticulocytes (MN-Trf-Ret). In a blood sample, separation of the very young reticulocytes from the mature erythrocytes makes this micronucleus assay possible. This investigation comprises three studies (cross-sectional, giving baseline data), two of which are connected to an intervention study. In the three cross-sectional studies (total number of subjects, 99) the frequency of MN-Trf-Ret (fMN-Trf-Ret) was measured and compared with the serum folate status. In two of the studies also serum homocysteine and Vitamin B12 were measured and compared with the baseline fMN-Trf-Ret. Combining the results from the three cross-sectional studies, a negative correlation between folate status and fMN-Trf-Ret was obtained (p < 0.05). The goal of the intervention studies was to clarify if different nutritional supplementations had any effect on the fMN-Trf-Ret and the cell proliferation (percentage polychromatic erythrocytes, PCE). Each of the two studies involved two groups, one placebo and one supplemented group. In one of the studies the supplementation was folic acid, 1000 mu g/day during 1 week(n = 30, both sexes); in the other intervention study, folic acid (800 mu g/day), B12 (20 mu g/day) and B6 (4 mg/day) were taken during I week (17 = 29, both sexes). No significant difference in %PCE or fMN-Trf-Ret between the two groups was found in either of the two intervention studies. (c) 2005 Elsevier B.V. All rights reserved.

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